Myths about myths about Thanksgiving turkey making you sleepy

Long answer is much, much more interesting than what you usually hear.

You have probably heard or read two types of contradictory stories:

In one type of story, eating a lot of turkey meat makes you sleepy. It is wrong in its conclusion because it makes (at least) two assumptions wrong.

In the other type of story, eating a lot of turkey meat does not make you sleepy. Its conclusion is correct, but not for the right reasons - it still (even the best article I could find) is likely to contain at least one erroneous assumption.

Both types of stories rely on the same underlying mechanism of how, potentially, this could work, based on what we know about human physiology. But both are ignoring (or are not aware) of a mechanism that is much more plausible. Turkey does not end up making you sleepy only due to that one little factoid that pro-sleepy stories get wrong and anti-sleepy stories get right.

Let's dissect this story, then. What are the essential lines that all (pro and con) stories have?

A) Tryptophan is an essential amino acid that we get from food. Tryptophan is a biochemical precursor of serotonin, i.e., our bodies convert tryptophan into serotonin in the brain.

B) Serotonin makes you sleepy.

C) More there is tryptophan in the body, more serotonin will be produced in the brain.

D) Since turkey meat has lots of tryptophan, eating it will result in sleepiness.

Pro-sleepy stories make all four assumptions. All four are wrong.

Most anti-sleepy stories make two or three of those four assumptions, thus they get at least one of them right. What the anti-sleepy stories usually get right is that D) is incorrect - it is a myth that turkey meat has much tryptophan. It actually has only about 509mg per 200-Calorie serving and is thus quite an average food (some other foods served at Thanksgiving may contain more tryptophan than turkey does).

At least some of the anti-sleepy stories also figure out that B) is wrong. Serotonin may make you happy or confident, but it cannot make you sleepy. Those articles get something important right: the amino-acid tryptophan is a precursor of neurotransmitter serotonin which in turn is the precursor of hormone melatonin. It is melatonin that makes you sleepy.

Here it is in a simplified shorthand:

What really derails both the pro-sleepy and anti-sleepy stories is the insistence that this all has to happen in the brain - the combined statements A) and C).

So they spend some time and effort figuring out how all that postulated extra tryptophan could possibly get into the brain. And that's hard - tryptophan does not passively pass the blood-brain barrier but is imported by a molecular carrier. The same carrier also transports other amino-acids. Thus one would have to ingest incredible amounts of pure tryptophan, no other molecules included, and somehow trick the carriers to transport all of the tryptophan into the brain, for this to work.

Once in the brain, that tryptophan would supposedly be turned into serotonin, and then serotonin would be turned into melatonin inside of the tiny pineal gland in the brain.

It appears that not everyone knows that all the enzymes needed for synthesis of melatonin (from tryptophan, via serotonin) can be found and are active in places other than just the pineal organ.

Conversion of tryptophan, via serotonin, to melatonin also happens in the retina of the eye, in the Harderian gland (located in the ocular orbit just behind the eyeball), and in the intestine.

The intestine has a large and complex semi-independent nervous system ("The Second Brain" of sensationalist reports) in which most or all of the same neurotransmitters and hormones are found as in the brain.

Actually, more melatonin is produced in the intestine than in all the other sites combined.

In most speciesintestinal melatonin gets degraded within the intestine. In other words, little or no melatonin ever leaves the intestine and leaks into the bloodstream.

Also, depending on the species, melatonin in the intestine is predominantly synthesized either during the day, or during the night, or continuously (Serotonin N Transferase enzyme is the "rate-limiting" enzyme in the pathway you see above in the picture, and it is under direct control of the circadian clock). In humans, it appears that some intestinal melatonin (not much, though) leaks into the bloodstream at all times, and that most of the synthesis happens during the day.

What happens if one ingests incredibly large amounts of pure tryptophan (not just tryptophan-rich food, where other molecules may interfere with the process)?

Interestingly, it has been shown in rats and chickens that adding extra tryptophan can promote synthesis of extra melatonin. In other words, the enzymes do not get saturated or down-regulated by extra tryptophan. Either there is a lot of enzymes already there, capable of processing extra tryptophan fast, or (we don't know yet) the enzymes may even get up-regulated by the tryptophan load.

In studies in which rats and chickens were loaded with huge amounts of pure tryptophan, extra melatonin leaks from the intestine into the bloodstream even if it normally does not do so in that particular species.

Other studies show that melatonin secreted from the intestine does not in any way affect the levels of melatonin synthesis in other locations (pineal, eye). If there is more melatonin, it came from the gut.

Melatonin does not require any carriers or transporters to cross the blood-brain barrier. No matter where it was originally produced, it easily enters the brain. Once there, it can produce sleepiness either directly or by acting on the circadian clock. It has long been known that increasing levels of melatonin in the bloodstream can phase-shift the circadian clock, place the phase into the night, and thus promote the feeling of sleepiness.

So, what anti-sleepy stories get right (and pro-sleepy stories get wrong), is that turkey is a weak agent for this. One would need enormous amounts of pure tryptophan to get an effect.

What both types of stories get wrong is their insistence that this has to happen in the brain. That is a wrong mechanism to look at - blood-brain barrier guards against extra tryptophan, so no amount of extra loading can do the trick.

But a huge load of tryptophan (how about a gallon of saturated solution poured directly into your stomach via gastric gavage?) could have the effect, and easily so, if one knows that all that extra tryptophan would first be converted into melatonin in the intestine itself, then easily pass into the brain. The mechanism is much more plausible, it is just that the turkey meat is incapable of triggering it.

So, why are you sleepy at the end of Thanksgiving dinner? You are tired of all that travel, cooking, hugging family, watching football, serving and eating... You are overstimulated. You may have had some alcohol with your meal. And look at the clock - it's almost bed-time anyway.

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